AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 6 612-L619, Copyright © 1994 by American Physiological Society
Ozone-induced release of cytokines and fibronectin by alveolar macrophages and airway epithelial cells
R. B. Devlin, K. P. McKinnon, T. Noah, S. Becker and H. S. Koren
Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park 27711.
Acute exposure of animals and humans to ozone results in decrements in lung
function, development of airway hyperreactivity, inflammation, edema,
damage to pulmonary cells, and production of several compounds with tissue
damaging, fibrinogenic or fibrotic potential. The contribution of airway
epithelial cells and alveolar macrophages to these processes is unclear. In
this study we have directly exposed human alveolar macrophages and human
airway epithelial cells to ozone in vitro and measured the cytotoxic
effects of ozone, as well as the production of the inflammatory cytokines
interleukin-6 (IL-6) and interleukin-8 (IL-8), and fibronectin, all of
which are substantially elevated in the bronchoalveolar lavage fluid of
humans exposed to ozone. Cells were grown on rigid, collagen-impregnated
filter supports, and the interaction of cells with ozone facilitated by
exposing them to the gas with medium below the support but no medium on top
of the cells. The results show that, although macrophages are much more
sensitive to ozone than epithelial cells, they do not produce increased
amounts of IL-6, IL-8, or fibronectin following ozone exposure. In
contrast, epithelial cells produce substantially more of all three proteins
following ozone exposure, and both IL-6 and fibronectin are secreted
vectorially. An immortalized human airway epithelial cell line (BEAS 2B)
was used in these experiments since human airway epithelial cells are
infrequently available for in vitro studies. Data from this study extend
previous findings which suggest that the BEAS cell line is a useful model
to study the interaction between airway epithelial cells and environmental
toxicants.
